| Ponce Monter et al.11 Ponce-Monter HA, Ortiz MI, Garza-Hernández AF, Monroy-Maya R, Soto-Ríos, M, Carrillo-Alarcón L, et al. Effect of diclofenac with B vitamins on the treatment of acute pain originated by lower-limb fracture and surgery. Pain Res Treat. 2012; 2012:104782.
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Randomized, controlled , Double-blind study |
122 patients aged between 18 and 55 yeras, with acute pain associated to lower limb fracture, VAS ≥50mm |
To compare the efficacy of diclofenac (75mg) associated to thiamine (100mg), pyridoxine (100mg) and cyanocobalamin (1mg), to diclofenac alone (same dose). Muscular injection 2 x/day, 24h before surgery and 24h after |
Decreased pain in the first 4h (VAS >30mm) in both groups. With association of vitamin B there has been further effectiveness as from 8h of the first application, being superiority maintained for 48h (p<0.05). Conclusion was that the association of vitamin B to diclofenac has increased its analgesic efficacy. |
| Mibielli et al.77 Mibielli MA, Geller M, Cohen JC, Goldberg SG, Cohen MT, Nunes CP, et al. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Curr Med Res Opin. 2009;25(11):2589-99.
|
Randomized, controlled , Double-blind study |
372 patients, mean age of 66 years, with acute low back pain |
To evaluate vitamins B1, 6 and 12 for pain. Randomization to diclofenac (50mg) + pyridoxine (50mg) + thiamine (50mg) + cyanocobalamin (1mg) (GDB), and diclofenac alone (50mg) (GD), by oral route 2x/ day, for no longer than 7 days. |
GDB has more effectively improved pain after 3 days, (decrease of ≥20mm in VAS), and there has been personal satisfaction in this group. GDB was also better for functionality and mobility (p<0.05) |
| Maladkar, Tekchandani, Dave1010 Maladkar M, Tekchandani C, Dave U. Post-marketing surveillance of fixed dose combination of methylcobalamin, alpha lipoic acid, folic acid, biotin, benfotiamine& vitamin b6-nutripathy for the management of peripheral neuropathy. J Diabetes Mellitus. 2014;4:124-32.
|
Open, exploratory, prospective, multicenter study |
497 patients aged between 40 and 75 years, with periphearl neuopathy of different origins |
To evaluate the efficacy and safety of the associations of methylcobalamin (1500μg), alpha-lipolic acid (200mg), folic acid (5mg), biotin (5mg), benfotiamine (50mg) and vitamin B6 (5mg), 1x/ day, O, for 12 weeks. |
Major improvement of neuropathic symptoms already in the 4th week. With 12 weeks there has been improvement in all symptoms (p<0.05): 78% pain decrease, 92.1% in numbness, 96.9% in muscle weakness, 96% in tingling and 99.2% in burning. The efficacy and safety of vitamin B associations for peripheral neuropathies was confirmed. |
| Negrão et al.1111 Negrão L, Almeida P, Alcino S, Duro H, Libório T, Melo Silva U, Figueira R, et al. Effect of the combination of uridine nucleotides, folic acid and vitamin B12 on the clinical expression of peripheral neuropathies. Pain Manag. 2014;4(3):191-6.
|
Open, exploratory, prospective, multicenter study |
212 patients aged between 19 and 92 years, with neuropathic pain of different origins |
To evaluate the efficacy of vitamin B12 (3μg) associated to uridine monophosphate (50mg) and folic acid (400μg) simultaneously with regular use of analgesics (paracetamol, tramadol and anti-inflammatory drugs), O 1x/day, forr 60 days. |
Significant pain improvement according to Pain Detect (from 17.5 to 8.8 points), and of analgesic consumption in 75.6% of patients. The conclusion was that the association of vitamin B12, uridine and folic acid was effective for pain and also has allowed lower analgesic consumption. |
| Talaei et al.1212 Talaei A, Siavash M, Majidi H, Chehrei A. Vitamin B12 may be more effective than nortriptyline in improving painful diabetic neuropathy. Int J Food SciNutr. 2009;60(Suppl 5):71-6.
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Randomized blind study |
100 patients between 18 and 53 years of age, with diabetic polyneuropathy |
To compare the efficacy of vitamin B12 and nortriptyline on neuropathic symptoms. Randomization for 2 groups: 2000μg vitamin B12, IM 2x/ week or nortriptyline 10mg at night, for 3 months. |
Better efficacy of vitamin B12 on pain, paresthesia and tingling, with statistical significance (p<0.001). without statistical significance in vibratory sensitivity, proprioception "pricking" and nervous conduction |
| Stracke et al.1313 Stracke H, Gaus W, Achenbach U, Federlin K, Bretzel RG. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diabetes. 2008;116(10):600-5.
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Randomized, controlled , double-blind study |
165 patients, aged between 42 and 73 years, with diabetic neuropathy |
To evaluate the efficacy and safety of benfotiamine (Bf). Randomization for 3 groups: Bf 600mg/day, Bf 300mg/day and placebo for 6 weeks |
Slight improvement of neuropathic symptoms with Bf, more pronounced with higher Bf dose. Conclusion was that Bf was a therapeutic option for diabetic polyneuropathy. |
| Xu et al.1414 Xu G, Lv ZW, Feng Y, Tang WZ, Xu GX. A single-center randomized controlled trial of local methylcobalamin injection for subacute herpetic neuralgia. Pain Med. 2013;14(6):884-94.
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Randomized, controlled , blind study |
98 patients, age ≥ 50 years, with sub-acute, moderate to severe post-herpetic neuralgia, for at least 120 days. |
To evaluate the efficacy of oral or local methylcobalamin for pain relief and DLA improvement. Randomization for 3 groups: methylcobalamin 1000μg SC 1x/day, lidocaine 1% SC 30mg 1x/day and methylcobalamin 0.5mg, O 3x/day, for 4 weeks. |
SC methylcobalamin has progressively decreased pain, with superiority of this route as compared to oral route or to lidocaine in continuous paroximal pain or alodynia. The conclusion was that SC methylcobalamin was potential choice for sub-acute post-herpetic neuralgia. |
| Xu et al.1515 Xu G, Xú G, Feng Y, Tang WZ, Lv ZW. Transcutaneous electrical nerve stimulation in combination with cobalamin injection for postherpetic neuralgia: a single-center randomized controlled trial. Am J Phys Med Rehabil. 2014;93(4):287-98.
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Randomized, controlled , blind study |
90 patients between 55 and 92 years, with post-herpetic neuralgia for at least 120 days and pain NS of >4 in dermatomes T6 to T10 |
To evaluate the efficacy of TENS combined to cobalamin applied in the painful area. Randomization for 3 groups: TENS + cobalamin, TENS + 1% lidocaine and TENS + colabamin (1000μg cobalamin 40mg lidocaine). SC application in the largest painful area after each TENS session, 6 days a week for 8 weeks. |
TENS + cobalamin or TENS + cobalamin + lidocaine have significantly improved pain (decrease ≥30%)(p<0.05). TENS + lidocaine have not significantly improved pain. There have been significant DLA increments with TENS + cobalamin and TENS + cobalamin + lidocaine, without statistically significant differences among them. |
| Xu et al.1616 Xu G, Lv ZW, Xu GX, Tang WZ. Thiamine, cobalamin, locally injected alone or combination for herpetic itching: a single-center randomized controlled trial. Clin J Pain. 2014;30(3):269-78.
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Randomized, controlled , blind study |
80 patients, age between 26 and 89 years, with com herpes zoster and pruritus score ≥4 for at least 20 days. |
To evaluate the efficacy of local cobalamin and thiamine on pain, itching and DLA. Randomization for 4 groups: thiamine (100mg), methylcobalamin (1000μg), 1% lidocaine (30mg) and thiamine associated to cobalamin (100mg+1000μg. SC injections, 6 days a week, for 4 weeks. |
There has been significant improvement in itching with thiamine, of pain with cobalamin and of both with the association of cobalamin and thiamine, in addition to improved DLA with cobalamin and cobalamin associated to thiamine. The conclusion was that thiamine had major anti-itching action, cobalamin analgesic action and the association of both had dual actions without synergy. |
| Chiu et al.1717 Chiu CK, Low TH, Tey YS, Singh VA, Shong HK. The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial. Singapore Med J. 2011;52(12):868-73.
|
Tandomized, controlled , double-blind study |
60 patients aged between 30 and 65 years, with non-specific chronic low back pain |
To evaluate the efficacy and safety of methylcobalamin on pain and incapacity according to Oswestry index. Randomization for methylcobalamin 500μg and placebo, by muscular route, 3x a week, for 2 months |
Methylcobalamin has significantly improved pain and incapacity as compared to placebo. Conclusion was that methylcobalamin was effective and safe for non-specific chronic low back pain. |
| Mibielli et al.1818 Mibielli MA, Nunes CP, Cohen JC, Scussel AB Jr, Higashi R, Bendavit GG, et al. Treatment of acute, non-traumatic pain using a combination of diclofenac-cholestyramine, uridine triphosphate, cytidine monophosphate, and hydroxycobalamin. Proc West Pharmacol Soc. 2010;53:5-12.
|
Randomized, controlled , double-blind study |
81 patients, age between 18 and 65 years, with non - traumatic acute pain in lumbar, cervical or hip region |
To compare the efficacy and safety of the association of diclofenac (70mg)/ cholestyramine, nucleotides (uridine 1.5mg and cytidine 2.5mg) and hydroxycobalamin (1mg) with the association of nucleotides (uridine 1.5mg and cytidine 2,5mg) and hydroxycobalamin (1mg), O, 2x/day, for 10 days. |
Pain improvement (decrease >30 mm in VAS) in approximately 87.5% of the diclofenac group (GD) and in 51.23% of the non-diclofenc group (GND), p>0.0006, improved functionality in 80% of GD and 29.3% of GND, p<0.0001. Conclusion was that GD was superior, but there has also been significant analgesia for GND |
| Garg, Syngle, Vohra1919 Garg S, Syngle A, Vohra K. Efficacy and tolerability of advanced glycation end-products inhibitor in osteoarthritis: a randomized, double-blind, placebo-controlled study. Clin J Pain. 2013;29(8):717-24.
|
Randomized, controlled , double-blind study |
30 patients between 43 and 72 years of age, with knee OA |
To evaluate efficacy and tolerability of the association benfotiamine (50mg), pyridoxamine (50mg) and methylcobalamin (500μg) as compared to placebo, O, 3x/day, for 24 weeks |
Statistically significant improvement of pain and clinical indices of disease activity, as well as decrease of one biomarker of disease activity (CRP) with vitamins. Conclusion was that the association of vitamins B1, 6 and 12 has improved funcionality on DLA and joint mobility |
| Magaña-Villa et al.2020 Magaña-Villa MC, Rocha-González HI, Fernández del Valle-Laisequilla C, Granados-Soto V, Rodríguez-Silverio J, et al. B-vitamin mixture improves the analgesic effect of diclofenac in patients with osteoarthritis: a double blind study. Drug Res. 2013;63(6):289-92.
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Randomized, controlled , double-blind study |
48 patients, between 59 and 68 years of age, with severe knee AO (pain NS >7) in the preoperative period of arthroplasty |
To evaluate efficacy and safety of diclofenac associated to vitamins B1, 6 and 12 (diclofenac 75mg, thiamine 100mg, pyridoxine 100mg and cyanocobalamin 5mg) compared to diclofenac (75mg) alone. Single muscular application 48h before surgery and pain evaluation for 12h |
Analgesic superiority of the association of vitamins B1, 6 and 12 to diclofenac. There has also been increased analgesic duration for diclofenac in the preoperative period of arthroplasty (p<0.05) |
